This is a Phase 1, open-label, multiple dose, single fixed-sequence, 2-period study to evaluate the effect of abrocitinib on the pharmacokinetics (PK) of caffeine, efavirenz and omeprazole in healthy adult participants. A total of approximately 13 healthy male and/or female participants will be enrolled in the study to obtain at least 12 evaluable participants who complete the study. Participants who withdraw from the study or are considered non-evaluable may be replaced at the discretion of the sponsor. Participants will be screened within 28 days of the first dose of study intervention. Participants will have a phone contact 3 days prior to Day 1 dosing (Day -3) in Period 1 as a reminder to abstain from caffeine-containing products. Participants will be admitted to the clinical research unit (CRU) at least 24 hours prior to Day 1 dosing (Day 1) in Period 1. Participants will remain in the CRU for a total of 15 days and 14 nights. Participants will have a telephone contact between 28-35 calendar days after the last administration of the investigational product.

Inclusion Criteria:

1. Participants must be ≥18 years of age at the time of signing the Informed consent document (ICD).
2. Male and female participants who are healthy as determined by medical evaluation including a detailed medical history, complete physical examination, laboratory tests, and cardiovascular tests.
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
4. Body mass index (BMI) of 17.5 to 32 kg/m2; and a total body weight >50 kg (110 lb).
5. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, neurological diseases, or other systems diseases, allergic diseases including drug allergies but excluding untreated asymptomatic seasonal allergies at the time of dosing
2. Subjects with moderate to severe gastroesophageal reflux disease (GERD) symptoms, or any condition affecting drug absorption e.g. gastrectomy, cholecystectomy
3. History of human immunodeficiency virus (HIV) infection, positive test for HIV, hepatitis B, hepatitis C, positive test for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCVAb). Subjects previously vaccinated for hepatitis B may be allowed. However, subjects vaccinated with vaccines having live or attenuated components within 6 weeks of the first dose of study drug, or expecting to be vaccinated during the course of the trial are excluded.
4. Any psychiatric condition including recent or active suicidal ideation or behavior, other psychiatric conditions that may increase the risk of study participation, or, in the investigator's judgement, make the subject inappropriate for the study.
5. Evidence or history of clinically significant dermatological conditions, e.g. atopic dermatitis (AD) or psoriasis, or visible rash present during physical examination, history of disseminated herpes zoster or disseminated herpes simplex, or localized dermatomal herpes zoster.
6. History of chronic infections, recurrent infections or latent infections, e.g. tuberculosis (TB); Positive QuantiFERONE® TB GOLD test, any acute infection within 2-weeks of baseline (Day-1).
7. Malignancies or history of malignancies except for adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
8. History of hypersensitivity, intolerance, or allergic reaction associated with prior exposure to caffeine, omeprazole, efavirenz and abrocitinib or any of their excipients.
9. Subjects who may be at increased risk if dosed with efavirenz, including severe hepatic impairment (Child Pugh Class C), or a history of seizures.
10. Use of prescription or non-prescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study drug; herbal supplements and hormonal contraceptives and hormone replacement therapy (HRT) must be discontinued at least 28 days prior to the first dose of the investigational product; Depo-Provera® must be discontinued at least 6 months prior to dosing with investigational product.
11. Systemic therapy with any of the medicines that are moderate or strong cytochrome P450 (CYP)1A2, CYP2B6, or CYP2C19 inhibitors within 28 days or 5 half-lives (whichever is longer), or moderate or strong CYP1A2, CYP2B6 or CYP2C19 inducers within 28 days or 5-half-lives (whichever is longer) prior to the first dose.
12. Previous administration with any investigational drug within 30 days (or as determined by local requirements), or 5-half-lives preceding the first dose of study drug intervention used in this study (whichever is longer).
13. Smokers and/or subjects who used nicotine-based products within three months prior to the first dose of the investigational product.
14. Screening supine blood pressure (BP)≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at last 5 minutes of supine rest. If BP≥140 mmHg (systolic) or ≥90 mmHg (diastolic), the BP should be repeated 2 more times and the average of the 3BP values should be used to determine the subject's eligibility.
15. Abnormal baseline standard 12-lead electrocardiogram (ECG), QT interval >450 msec, QTcF>450 msec, . If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the subjects eligibility. Computer-interpreted ECGs should be 0ver-read by a physician experienced in reading ECGs before excluding a subject.
16. Subjects with abnormal blood chemistry; abnormal hematology including complete WBC count and differentials; estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2
17. History of alcohol abuse, binge drinking, or any illicit drug use or dependence within 6 months of screening. Positive urine drug test.
18. Pregnant females, breastfeeding females, female subjects of childbearing potential who are unwilling or unable to use one highly effective method of contraception as outlined in the protocol for the duration of the study and for at least, 28 days after the last dose of study intervention. Unwilling to comply with lifestyle considerations in the protocol.
19. Subjects who routinely consume more than five 8-ounce cups of coffee (or caffeine equivalent), or greater than 6 servings (1 serving is approximately equivalent to 125 mg of caffeine) of tea, cola or other caffeinated beverage per day.
20. Consumption of chocolate and chocolate-containing products (e.g. hot chocolate, ice cream, cookies, etc) within 48 hours prior to the first dose of study drug and during the study.
21. Consumption of charcoal-broiled beef within 7 days prior to the first dose of study drug as it is known to induce CYP1A2 enzyme.
22. Consumption of cruciferous vegetables (e.g. cauliflower, broccoli, Brussel sprouts and cabbage) within 7 days prior to the first dose of study drug as cruciferous vegetables are known to increase CYP1A2 activity
23. Blood donation (excluding plasma donation) of approximately 1 pint (500 ml) or more within 60 days prior to dosing.
24. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator and their respective family members.

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

All enrolled participants who received at least 1 dose of study intervention.

Up to 48 days after the first dose in period 1. This includes 3 days of period 1, 10 days of period 2 and 28-25 days of the follow-up period.

The same event may appear as both an AE and an SAE. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.

In addition to the initial 13 participants, this study enrolled 13 replacement participants as some of the PK samples from Day 8 Period 2 collected from the initial 13 participants were lost in transit and remaining samples were not evaluable. This replacement is consistent with the protocol.